Pulsed magnetization transfer spin-echo MR imaging

Cross relaxation between macromolecular protons and water protons is known to be important in biologic tissue. In magnetic resonance (MR) imaging sequences, selective saturation of the characteristically short T2 macromolecular proton pool can produce contrast called magnetization transfer contrast, based on the cross-relaxation process. Selective saturation can be achieved with continuous wave irradiation several kilohertz off resonance or short, intense 0° pulses on resonance. The authors analyze 0° binomial pulses for T2 selective saturation, present design guidelines, and demonstrate the use of these pulses in spin-echo imaging sequences in healthy volunteers and patients. Using the phenomenologic Bloch equations modified for two-site exchange, the authors derive the analytic expressions for water proton relaxation under periodic pulsed saturation of the macromolecular protons. This relaxation is shown to be monoexpo-nential, with a rate constant dependent on the saturation pulse repetition rate and the individual and cross-relaxation rates.     

Infertility: Avoidance of triplet pregnancies by elective transfer of two good quality embryos

Attempts to increase the probability of a successful pregnancyin in-vitro fertilization (IVF) treatment by increasing thenumber of embryos transferred automatically also increase theprobability of multiple pregnancies and their attendant risks.Even where the number of transferred embryos is limited to amaximum of three as in this and other centres, there is a highincidence of twins and triplets. The question therefore ariseswhether the number of transferred embryos should be furtherlimited to a maximum of two in cases where the prognosis isotherwise good. The only objection to this idea is a possiblelowering of pregnancy rate. The present study set out to investigatethis question. No significant lowering of pregnancy rate wasfound, so that limiting the number of transferred embryos totwo where the prognosis is otherwise good has now become standardpractice in our centre. A good IVF prognosis was defined bythe following criteria: first attempt for IVF, less than 37years old, and good embryo development. From 183 patients fulfillingthese criteria, 80 agreed to the transfer of two embryos (group1) and 103 opted for a triple transfer (group 2). Patient characteristicsand embryology results were similar in the two groups. In group1, 34 patients (42.5%) became pregnant and in group 2, 50 (48.5%).This difference is not significant. Similarly, twin pregnancyrates in both groups were high; eight twin pregnancies (23.5%)in group 1 and 12 (24%) in group 2. For the triplet pregnancyrate of 18% (nine triplet pregnancies) in group 2, there wasobviously no parallel in group 1. After thawing about half ofthe cryopreserved embryos and subsequently replacing them, preliminarycumulative pregnancy rates of 52.5% in group 1 and 53.4% ingroup 2 were obtained. Future results from cryopreservationshould provide relatively better outcomes for group 1 sinceall the patients in this group had at least one embryo frozenand fewer embryos replaced in the fresh cycle.     

In vivo 31P NMR studies of paraplegics' muscles activated by functional electrical stimulation

The bioenergetics of paralyzed muscles of spastic paraplegic patients under functional electrical stimulation (FES) was studied in vivo using ³¹P NMR. The protocol included rest, 3 min of induced tetanic isometric contraction through surface electrodes and 40 min of recovery. The continuous stimulation, the force recording and the ³¹P NMR measurements were sampled simultaneously inside the whole body imager. Normal values were found for the phosphorous metabolite ratios at rest. During contraction, prominent changes were detected including: a) accumulation of inorganic phosphate (P) accompanied by an unusually strong signal in the phosphomonoester (PME) region, b) phosphocreatine (PCr) decline, and c) a decrease in the intracellular pH. In the following recovery period the physiological state of the muscle was monitored and quantitated by ³¹P NMR. No metabolic and mechanical irreversible damage was detected in the paraplegics' muscles activated by FES under our experimental conditions.     

Is monoamine oxidase inhibitor induced myoclonus serotoninergically mediated?

Summary In the present study a single case observation of myoclonus during sleep-wave transition was monitored in a depressed patient treated with the monoamine oxidase inhibitor, phenelzine. The myoclonus had a rhythm of 1 c/second and lasted for two years, the duration of phenelzine treatment. Myoclonus appeared neither during wakefulness nor during sleep, but at wake-sleep-wake transitions. This switch myoclonus was associated with phasic muscle hyperactivity during REM sleep.Methysergide a 5-HT suppressor, decreased the switch myoclonus frequency and the REM muscle hyperactivity, indicating serotoninergic involvement in the mechanism of phenelzine induced myoclonus.     

Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells

Summary Impairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid -glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral -glucosidases do not seem influencial. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a high-uptake form of acid -glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed.     

The depressing effect of tetracaine and ryanodine on the slow outward current correlated with that of contraction in voltage-clamped frog muscle fibres

The effects of tetracaine (10–50 M) and ryanodine (0.1–10 M) were tested on the slow outward K⁺ current (I _so) and the mechanical tension of isolated frog muscle fibres in a voltage-clamp device (double mannitol-gap) connected to a mechanoelectric transducer. In the concentration range tested, both drugs induced a simultaneous inhibition of tension and current. In all cases the effect on tension was twice that on current. The tetracaine-induced current and tension blocks were fully reversible and dose-dependent. In contrast the ryanodine effects on current and tension were not reversible and did not exhibit a dose dependence except for the delay before the onset of the response, which was shortened when the concentration was raised. Linear regression analysis of the time-dependent and dose-dependent effects of both drugs indicated a strong correlation between the decreases in tension and current. It is concluded that the slow outward current is partly under the control of the Ca²⁺ release from sarcoplasmic reticulum during contraction.     

Gene therapy of malignant brain tumors: a rat glioma line bearing the herpes simplex virus type 1-thymidine kinase gene and wild type retrovirus kills other tumor cells.

Tumor cells infected with a retrovirus vector (VIK) containing the herpes simplex virus thymidine kinase (HSV-TK) gene can be selectively killed by treatment with nucleoside analogues, such as ganciclovir. To mediate delivery of the HSV-TK gene to "recipient" tumor cells, "donor" C6 rat glioma cells infected with the VIK vector (C6VIK) were superinfected with wild type Moloney murine leukemia virus (WT Mo-MLV). These modified donor cells (C6VIKWT) produced both wild type retrovirus and the VIK vector. In culture, C6VIKWT cells were 300-fold more sensitive to the toxicity of ganciclovir than were C6VIK cells, suggesting that the presence of wild type retrovirus contributed to the toxicity. Co-culture of C6VIKWT cells with the C6 subline, C6BAG, sensitized the latter to ganciclovir treatment. Nude mice inoculated subcutaneously with a mixture of C6VIKWT and C6BAG cells showed regression of subsequent tumors when treated with ganciclovir. The observations show that tumor cells modified in culture by infection with a retrovirus bearing the HSV-TK gene and wild type retrovirus are not only sensitive to ganciclovir, but can transfer this sensitivity to neighboring "naive" tumor cells in culture and in vivo.     

Plateau potentials evoked by climbing-fibre stimulation are restricted to the Purkinje cell dendrites of the cat

The present study investigated the duration of afterdepolarizations in Purkinje cell somata following climbing-fibre activation. Intracellular recordings revealed that, in cells with membrane potentials more negative than -50 mV and with normal spike-generating capabilities, climbing-fibre activation resulted in somatic responses with short afterdepolarizations. As the cell deteriorated and the resting membrane potential became more positive, the duration and form of the climbing-fibre response resembled the plateau potentials recorded from proximal dendrites. The absence of plateau potentials in undamaged Purkinje cell somata was confirmed by extracellular recording of test spike amplitudes following evoked climbing-fibre responses.     

Intermediate filament expression in human vascular smooth muscle and in arteriosclerotic plaques

Summary Different regions of human aorta and of other human arteries obtained at autopsy were analyzed with regard to their topography and to the different stages of arteriosclerosis. Material was studied by immunocytochemical techniques with antibodies specific for either desmin (D) or for vimentin (V), the two types of intermediate filament proteins present in vascular smooth muscle cells. In normal arteries endothelial cells as well as the adjacent intimal cells were D–V+. In the media D+V+ as well as D–V+ cells were present, with the relative numbers of each cell type dependent on the particular blood vessel. When cells in arteriosclerotic plaques at different stages of development were examined an occasional plaque showed cells of the D+V+ type. In the majority of plaques however the cells were V– D+. In plaques where severe ulceration and necrotic material was present D–V+ cells were found at the border of the lesion: foam cells when they could be identified appeared to be D–V+.     

Intramuscular pressure,EMG and blood flow during low-level prolonged static contraction in man

Seven men performed one-legged isometric knee-extension at 5% MVC for 1 h. Intramuscular pressure increased with contraction from its resting value of 14 (2–31) mmHg. Some intramuscular pressure recordings stayed at an almost constant level throught the 1 h contraction, but most recordings showed large fluctuations from resting values up to 90 mmHg. The overall mean intramuscular pressure was twice the resting value. In some cases, EMG recordings confirmed that the changes in intramuscular pressure were related to alternating recruitment of various parts of the knee-extensors. Blood flow in the femoral vein increased within 3 min of 5% MVC to a level of 1.58 (1.25-2.22) 1 min^-1 and no significant changes occurred during the 1 h contraction. In two subjects blood flow was measured also in the recovery period, and this decreased almost immediately when the muscle relaxed. It is concluded that during low-level static contractions, the blood supply to the exercising muscle is maintained at a sufficiently high level, and that the alternating recruitment of muscle fibres may result in a heterogeneously distributed blood flow within the contracting muscle. Despite this the muscle was fatigued after the 1 h at 5 % MVC. The rating of perceived exertion (RPE) increased from 1.9 (1–3) at the beginning to 4.5(2–8) at the end of contraction, and MVC was decreased by 12% after the contraction.